OBJECTIVE: Deficiencies of vitamin A and iodine are common in many developing countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism. The study aim was to investigate the effects of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats. DESIGN: Weanling rats (n = 56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin A and iodine (VAD + ID group), or sufficient in both vitamin A and iodine (control) for 30 days in a pairfed design. Serum retinol (SR), thyroid hormones (FT(4), TT(4), FT(3), and TT(3)), serum thyrotropin (TSH), pituitary TSHbeta mRNA expression levels, and thyroid weights were determined at the end of the depletion period. MAIN OUTCOME: Compared to the control and ID groups, SR concentrations were about 35% lower in the VAD and VAD + ID groups (p < 0.001), indicating moderate VA deficiency. Comparing the VAD and control groups, there were no significant differences in TSH, TSHbeta mRNA, thyroid weight, or thyroid hormone levels. Compared to the control group, serum TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.05), and FT4 and TT4 were lower (p < 0.001), in the VAD + ID and ID groups. Compared to the ID group, TSH, TSHbeta mRNA, and thyroid weight were higher (p < 0.01) and FT(4) and TT(4) were lower (p < 0.001) in the VAD + ID group. There were no significant differences in TT3 or FT3 concentrations among groups. CONCLUSION: Moderate VAD alone has no measurable effect on the pituitary-thyroid axis. Concurrent ID and VAD produce more severe primary hypothyroidism than ID alone. Objective: Deficiencies of vitamin A and iodine are common in many developing countries. Vitamin A deficiency (VAD) may adversely affect thyroid metabolism. The study aim was to investigate the effects of concurrent vitamin A and iodine deficiencies on the thyroid-pituitary axis in rats. Design: Weanling rats (n ϭ 56) were fed diets deficient in vitamin A (VAD group), iodine (ID group), vitamin A and iodine (VAD ϩ ID group), or sufficient in both vitamin A and iodine (control) for 30 days in a pair-fed design. Serum retinol (SR), thyroid hormones (FT 4 , TT 4 , FT 3 , and TT 3 ), serum thyrotropin (TSH), pituitary TSH mRNA expression levels, and thyroid weights were determined at the end of the depletion period. Main outcome: Compared to the control and ID groups, SR concentrations were about 35% lower in the VAD and VAD ϩ ID groups (p Ͻ 0.001), indicating moderate VA deficiency. Comparing the VAD and control groups, there were no significant differences in TSH, TSH mRNA, thyroid weight, or thyroid hormone levels. Compared to the control group, serum TSH, TSH mRNA, and thyroid weight were higher (p Ͻ 0.05), and FT 4 and TT 4 were lower (p Ͻ 0.001), in the VAD ϩ ID and ID groups. Compared to the ID group, TSH, TSH mRNA, and thyroid weight were higher (p Ͻ 0.01) and FT 4 and TT 4 were lower (p Ͻ 0.001) in the VAD ϩ ID group. There were no significant differences in TT 3 or FT 3 concentrations among groups. Conclusion: Moder...